Where do clinicians begin?  Begin with assessment of family history “Even when an individual’s genome can be displayed on a personal microchip, interpreting that information will depend in large part, on the biological and environmental contexts in which the genome is expressed, and the family milieu is as good a guide as any.” Pyeritz RE. JAMA 278:235. 1997

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Family Health History  Is an important risk factor for chronic diseases that reflects – Inherited genetic susceptibility – Shared environment risk factors (diet) – Cultural factors (religious practices) – Common behaviors (smoking, physical activity)  Prior to offering any genetic susceptibility testing, a clinician needs to assess the family history of disease – Who should be tested? – What genes should be tested?

Family History of Diabetes  T2D is an independent risk factor for the disease  88-95% have affected 1 st degree relatives – 70-77% have affected 2 nd degree relative  Individuals with a positive family history are about 2-6 times more likely to develop T2D than those with a negative family history – Risk ~40% if 1 T2D parent; ~80% if 2 T2D parents

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Family History of Diabetes  FH identifies a group of high risk individuals – Using a simple and inexpensive approach – Who may benefit from early detection – To develop personal and family-based risk factor modification strategies – In the future, may benefit from genetic testing  Has been difficult to find genes for T2D – Late age at onset – Polygenic inheritance • Multiple genes with small effects – Multifactorial inheritance

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